Many people engagingin medical scienceasked me,"You’ve beenworking on the exploration of Holistic Integrated Medicine（HIM）for quite awhile.What is the progressyou have made in your research?Have you got your article published?May I beyour first reader?"
Supplementary Methods Supplementary Figure 1-5 Supplementary Table 1-2
Background: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.Methods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged >= 18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.Findings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 261 months (95% CI 221-318; 149 [52%] of 284 died) versus 133 months (105-162; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 057, 95% CI 046-071; p<00001), median progression-free survival was 81 months (95% CI 62-88; 214 events occurred) in the cemiplimab group versus 53 months (43-61; 236 events occurred) in the chemotherapy group (HR 051, 95% CI 042-062; p<00001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 66 months (61-93) and overall survival of 151 months (113-187). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signalsINTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.Copyright (c) 2023 Elsevier Ltd. All rights reserved.
Objective To investigate the problems existing in pain treatment of cancer patients from outpatient depart-ment and to explore the value of clinical pharmacists in pain treatment of cancer patients.Methods Patients with cancer pain who visited the pain relief clinic of Cancer Hospital of Chinese Academy of Medical Sciences between June 2019 and September 2020 were included in this study.Clinical pharmacists conducted medication education and pain perception sur-vey on their first day of treatment,followed up the problems existing in the pain treatment after 2 weeks and provide phar-maceutical service.Results 63 patients with cancer pain participated in the follow-up,and 51 patients were finally select-ed.Most of them were patients with chest tumors,gastrointestinal tumors and gynecological tumors.The most common prob-lems in patients'analgesic treatment included"poor analgesic effect","intolerable adverse drug reactions"and"worrying about drug addiction".73%of patients said they would endure pain,65%would use the minimum dose of painkillers,and 49%were worried about the addiction of painkillers.Clinical pharmacists provided pharmaceutical services for 71%of pa-tients,including suggestions for dosage adjustment(15%),introduction to drug literacy(17%),education on drug use(20%),suggestions on adverse reaction management(22%),and suggestions for follow-up visits(26%).Conclusion There were still many deficiencies in the management of cancer pain patients in the outpatient department,such as unsatisfactory analgesic effect,insufficient drug knowledge,and cognitive deviation of pain relief.Clinical pharmacists should participate in the whole process management of cancer pain patients in the outpatient department,and continue to strengthen medica-tion education for patients.
Objective To investigate the characteristics,management and immunotherapy rechallenges of immune checkpoint inhibitor-induced diabetes mellitus(ICI-DM).Methods We reported four cases of patients with new-onset DM during ICI treatment,and provide a systematic review of all published cases(PubMed/Web of Science/CNKI/VIP/Wanfang databases)of autoimmune diabetes mellitus related to ICI therapy.The four cases in our hospital were pooled with cases previously reported in the literature.Results A total of 187 cases were included,of which 71.7%were treated with pro-grammed death-1(PD-1)inhibitors,and the ICI-DM occurred with a median time of 14 weeks after the medication.The presence of pancreatic autoantibodies was associated with a shorter time to the onset of DM[(4.10±33.7)vs.(22.86±19.16)weeks,P=0.032)].Diabetic ketoacidosis(DKA)was the first symptom in 75.4%of the ICI-DM patients.65.8%of the ICI-DM patients were diagnosed due to emergency admission,and 34.3%were accompanied with other immune-related endo-crine adverse reactions.Glycemic index was controllable in 66.8%patients after insulin replacement therapy,and 36.9%of the patients restarted immunotherapy.Conclusion ICI-DM has the characteristics of insidious onset and high probability of ketoacidosis.Regular monitoring of blood glucose and timely endocrine examination in case of hyperglycemia is recom-mended.
Objective To analyze the adverse reactions of olaparib in the treatment of ovarian cancer in the real-world,as well as the influencing factors of anemia,the most common hematological adverse reaction.Methods This study retrospective-ly analyzed the adverse reaction data,with a particular focus on the incidence of anemia,from a cohort of 146 ovarian can-cer patients who received olaparib treatment at our institution between July 2018 and October 2022.The factors associated with grade≥3 anemia were assessed through both univariate and multivariate analyses.Results During the treatment peri-od,the overall incidence rate of adverse effects was found to be 76.7%.Furthermore,the incidence rate of grade≥3 adverse reactions was 37.0%,with anemia(31.5%)being the most prevalent.Notably,the incidences of grade≥3 anemia were ob-served to be respectively 60.5%,16.3%,and 23.2%within the first 3 months,4～6 months,and 6 months after initiating treatment.Remarkably,the discontinuation of medication due to anemia persisted at a rate of 11.6%even after 1 year treatemnt.The results of the multivariate logistic regression analysis indicated that age(χ2=7.914,P=0.005,OR=1.066)and grade≥3 anemia during prior platinum-containing chemotherapy(χ2=5.269,P=0.022,OR=3.563)were identified as the in-dependent risk factors for grade≥3 anemia during the maintenance treatment of olaparib.Conclusion In the context of real-world ovarian cancer treatment with olaparib,anemia emerges as the predominant hematological adverse reaction,particularly of grade 3 and higher severity,and it significantly contributes to the treatment discontinuation.It is crucial to recognize that the risk of anemia during maintenance therapy extends beyond a three-month period and necessitates ongoing vigilance.Age and previous grade≥3 anemia during platinum-containing chemotherapy are identified as significant risk factors for the devel-opment of severe anemia during olaparib maintenance therapy.Consequently,it is imperative to enhance the monitoring of these high-risk groups in order to mitigate the occurrence of severe adverse events.
Objective To establish the assessment for extended application of tislelizumab in the first-line treatment of advanced gastric cancer,so as to provide basis and reference for clinical rational application.Methods Review the litera-ture and collect the data of clinical trials related to PD-1 monoclonal antibody used in the first-line treatment of advanced gastric cancer.Analyze the results of clinical trials by entropy weight method and TOPSIS method,and evaluate the effec-tiveness and safety of tislelizumab in the first-line treatment of advanced gastric cancer.WHO/HAI standard survey meth-od was used to evaluate the accessibility of tislelizumab.Based on the evaluation results of effectiveness,safety and accessi-bility,the opinions on the extended application were given.Results Tislelizumab combined with chemotherapy had good ef-fectiveness,safety and accessibility for first-line treatment of advanced gastric cancer.Its application could be extended when necessary in combination with clinical practice.Conclusion Tislelizumab can be considered as an extended first-line treatment for advanced gastric cancer under appropriate circumstances.
Objective To explore the clinical feature and treatment of pembrolizumab-induced persistent severe throm-bocytopenia.Methods Taking a case of pembrolizumab-induced persistent grade 4 thrombocytopenia as an entry point,the clinical characteristics and treatment plan were analyzed by reviewing the literature.Results The data showed that the inci-dence was very low of severe thrombocytopenia caused by pembrolizumab.Some patients had poor effect after immunosup-pressive therapy such as glucocorticoid and cyclosporine.The reason may be related to the autoimmune abnormalities re-sulted by the failure of"immune brake"in vivo after repeated use of programmed death-1(PD-1)inhibitors.Conclusion Clinicians should weigh up the pros and cons,and closely monitor platelet counts,so as to ensure the medication safety of patients.
Pain is one of the most common and unbearable symptoms in cancer patients.Precise and standard drug ther-apy is an effective means of cancer pain control,and good medication literacy of cancer pain patients is the key to pain con-trol.In recent years,studies on the relationship of analgesic drug use with pain control and medication literacy of cancer pa-tients have been gradually carried out.In this paper,the concept of medication literacy,assessment tools,influencing fac-tors and other aspects of cancer pain patients were reviewed,aiming to improve the current status of pain control disorders,promote the safety of self-medication,and improve the ability of self-pain management.
Cell proliferation and cell death are fundamental processes that control the growth and development of the whole living organisms.The abnormal regulation of cell proliferation and cell death result in the uncontrolled and continu-ous proliferation of cells,which become the characteristic of cancer.Initially,it was thought that cell death was a common tumor suppressor mechanism,and this property was used in cancer therapy.However,with the increasing understanding of cell death,it has been found that dead cells can promote tumor cell proliferation,which in turn leads to tumor progression.Therefore,this article briefly reviewed the research status of several different regulatory cell death(RCD)in tumor cell pro-liferation,including apoptosis,pyroptosis and autophagy,and summarized the in-depth understanding of how these cell death modes as a"double-edged sword"affect cell proliferation through the cell cycle,in order to provide theoretical basis and new ideas for the prevention and treatment of cancer.
Objective To study the effect of astragalus injection on the immune function of leukemia patients after che-motherapy,and to analyze and evaluate the related factors.Methods A total of 100 patients with leukemia admitted to our hospital between January 2016 and January 2019 were included in this study,and were divided into astragalus group and control group by random envelope method.Patients in the control group received conventional VDP chemotherapy,while those in the astragalus group received astragalus injection plus conventional VDP chemotherapy.The clinical efficacy,changes of immune function before and after chemotherapy,quality of life score and incidence of adverse reactions were compared between the two groups.In addition,Logistic regression was used to analyze the factors affecting the post-chemo-therapy infection of leukemia patients.Results The clinical effective rate of astragalus group was higher than that of con-trol group(P<0.05).After chemotherapy,CD3+,CD4+ levels and the CD4+/CD8+ in the astragalus group were all higher than those in the control group(all P<0.05).The incidence of nausea,vomiting,hyperhidrosis,bleeding and infection in the as-tragalus group was lower than that in the control group(all P<0.05).Logistic regression analysis results showed that age,poor immune function and non-use of astragalus injection were independent risk factors for infection after chemotherapy in leukemia patients(all P<0.05).Conclusion Astragalus injection can effectively improve the effect of chemotherapy in pa-tients with leukemia,alleviate the impact of chemotherapy on patients'immune function,and reduce the risk of chemothera-py-related adverse reactions.In addition,with the increase of age,the decline of immune function and the non-use of as-tragalus injection would increase the incidence of infection after chemotherapy,which is worthy of clinical attention.
Tumor immune escape plays a key role in the occurrence and development of hematological malignancies.At present,immunotherapy has become a research focus.CD47 is a highly glycosylated transmembrane protein widely ex-pressed on the surfaces of normal cells and tumor cells.Combined with the signal regulatory protein α(SIRPα),thrombos-pondin 1(TSP-1)and integrin,CD47 plays an important role in inflammation and tumor immune escape.CD47 on the sur-faces of tumor cells binds to the SIRPα on the surfaces of macrophages,inhibiting the phagocytosis of macrophages and pro-ducing tumor immune escape,thus promoting the occurrence and development of hematological malignancies.It has been proven in a variety of hematological malignancies that overexpression of CD47 is associated with poor prognosis.Many drugs targeting CD47 are undergoing preclinical and clinical studies in many types of hematological malignancies,and some of the drugs have shown good safety and promising efficacy.This paper summarizes the structure and function of CD47,the relation between CD47 and tumor-associated macrophage(TAM),the role of CD47 in immune escape of hemato-logical malignancies,and the research progress of CD47-targeted drugs.
Objective To investigate the effects and mechanism of tetramethylpyrazine(TMP)on the proliferation and apoptosis of human colorectal cancer SW480 cells.Methods The human colorectal cancer SW480 cells in logarithmic growth phase were interfered with DMSO(blank control group),different concentrations of TMP(50,100,200 μg·mL-1)and L-OHP(25 μg·mL-1)for 48 h.Then the proliferation activity of SW480 cells in each group was detected by MTT,and the cloning ability of SW480 cells was observed by cell cloning experiment.The cell cycle,apoptosis and protein expression were detected by flow cytometry or Western blotting.Results Compared with blank control group,treatment with TMP(50,100,200 μg·mL-1)or L-OHP(25 μg·mL-1)could decrease the proliferation activity of SW480 cells,and increase the apop-tosis rate.Treatment with TMP(100,200 μg·mL-1)or L-OHP(25 μg·mL-1)could significantly inhibit the cell cloning abil-ity,block cell cycle in G0/G1 phase,increase the expression of PTEN,Cleaved Caspase-3,Bax,P27 and the ratio of Bax/Bcl-2,decrease the expression of p-Akt,cyclin D1,Bcl-2 and Akt phosphorylation rate,and all of the differences were statistically significant(P<0.05).Compared with L-OHP(25 μg·mL-1)treatment group,the proliferation activity of SW480 cells was decreased,the cell apoptosis rate increased,the expression of PTEN,Bax,P27 and the ratio of Bax/Bcl-2 increased,and the expression p-Akt,cyclin D1 and Akt phosphorylation rate decreased in the TMP 200 μg·mL-1 treatment group(P<0.05).Conclusion TMP may inhibit the PI3K/Akt pathway by upregulating the expression of PTEN,so that could in-hibit the proliferation and promote the apoptosis of SW480 cells.
Objective To study the effects of extract of Bruguiera sexangula leaves on the proliferation,apoptosis,inva-sion and migration of non-small cell lung cancer A549 cells.Methods Non-small cell lung cancer A549 cells were divided into Control group(treated with 0 μg·mL-1 extract of Bruguiera sexangula leaves),BSLE-L group(treated with 10 μg·mL-1 extract of Bruguiera sexangula leaves),BSLE-M group(treated with 20 μg·mL-1 extract of Bruguiera sexangula leaves),BSLE-H group(treated with 30 μg·mL-1 extract of Bruguiera sexangula leaves),BSLE-M+Jagged1-Fc group(treated with 20 μg·mL-1 extract of Bruguiera sexangula leaves and Notch signaling pathway activator Jagged1-Fc).MTT experiment was used to detect the proliferation of cells,and plate cloning experiment to detect the cell clone formation ability,flow cytometry to detect the cell apoptosis changes,Transwell chamber to detect the cell migration and invasion ability,Western blotting to detect the expressions of Bax,Bcl-2,vimentin,E-cadherin,MMP-2,Notch-1,NICD-1 and Hes-1 proteins.Results Com-pared with the Control group,the cell survival rate and the number of clone formation and the number of invasion and migra-tion cells decreased sequentially in the BSLE-L,BSLE-M and BSLE-H groups.The expression levels of Bax and E-cad-herin proteins in cells increased sequentially in the BSLE-L,BSLE-M and BSLE-H groups,and the expression levels of vi-mentin,MMP-2,Bcl-2,Notch-1,NICD-1 and Hes-1 proteins decreased(P<0.05).Compared with the BSLE-M group,the survival rate and the number of cell clone formation,and the number of migration and invasion cells increased significantly in the BSLE-M+Jagged1-Fc group,while the cell apoptosis rate decreased significantly.The expression levels of Bax and E-cadherin proteins in the cells were down-regulated,while the expression levels of Bcl-2,vimentin,MMP-2,Notch-1,NICD-1,Hes-1 proteins were up-regulated(P<0.05).Conclusion Bruguiera sexangula leaves extract inhibited the prolifer-ation,invasion,migration and EMT of non-small cell lung cancer A549 cells,and induced cell apoptosis.The mechanism was related to the decrease of the activation level of Notch signal.
自1960年以来,美国FDA推出的基础研究-发现-设计-临床前开发-临床研究等过程的新药研发的转化研究,这种"万里挑一"的转换研究模式在生命科学研究领域得到快速的发展."精准医学"概念和计划,希望更接近治愈癌症和糖尿病等疾病,希望将以基因为特点的大数据信息用于精准个体化药物治疗."精准医学"作为医学的未来是人类医学的变革,长期目标是为实现多种疾病的治愈提供有价值的信息.基于精准医疗四要素中"精确、准时、共享、个体化",提出"精准药学"的概念,希望它在实现"精准医疗"中发挥作用,而且具有不同于"精准医学"的研究目标和研究特征."精准药物"治疗只有在实现"精准诊断"的基础上,医疗应用相关的"精准药物"才能提出"精准治疗方案",才能实现精准的个体化治疗. 创新研究各个环节对新药研发均有影响,如:(1)靶点不一定能用于药物发现,有"活性"化合物不一定能成药;(2)动物疾病模型与人疾病的生物标志物的不一致性,不能预见临床的有效性和安全性;(3)动物安全性评价结果不能有效地预测药物的安全性;(4)临床试验受试者的结果不具备显著的代表性;(5)新医药产品的出现还无可靠的评价的工具和标准;等等.基因组学告诉我们什么可能会发生,蛋白质组学告诉我们什么将要发生,代谢组学则告诉我们什么已经发生!因此基于组学量大的特点,精准地认识组学和用好组学,对于新药的研发和推进精准医疗发展有重要的作用.在"大数据"时代,药物研发可以认为与健康人和患者的基因有关,更与疾病的病因、进程、环境、保健等有关,也与药物的多技术组合的成功有关,因此需要更广博的知识和广阔的视野去认识研发的难度和精准性. 从目前的科学认识来看,真正"治愈"癌症任重道远,它不应局限于药物治疗,攻克癌症需要发现更有效的疗法.在一定程度上,预防是强有力的治愈癌症之良策,环境安全、食品安全、健康科普、良好的生活习惯和有度的运动保健也十分重要.通过本文的阐述,我们寄希望于精准药物研发、精准诊断的发展和精准医疗的发展,通过大数据共享,能改变这类"75%无效"和"基本不靠谱"的局面.但是我们也认为对于癌症治疗的科学发展任重道远.药物仅仅是一种手段,对于癌症,有效药物是必要的,"没有药物是万万不能的",但是没有精准药物、精准诊断和精准治疗,"药物也不是万能的".精准医学真实世界也很复杂.记住默克先生所说:在我们找到一条有效途径,把我们的最佳成果带给每一个人之前,我们决不能停下来.
Thymic epithelial tumor(TET)is a rare mediastinal malignant tumor.Due to the lack of randomized con-trolled trials,there is no standard treatment in China at present.Surgical resection is the first choice for TETs in early stage,but for unresectable,recurrent or metastatic advanced TETs,comprehensive medical treatment is mainly adopted,including chemotherapy,targeted therapy and immunotherapy.National Comprehensive Cancer Network guidelines recommend plati-num-based combination chemotherapy,but the efficacy is not satisfactory.In recent years,with an in-depth understanding of biology of TETs,more and more studies have focused on the use of immune checkpoint inhibitors(ICIs)such as anti-pro-grammed death 1(PD-1)/programmed death ligand-1(PD-L1)antibodies in TETs.However,due to the unique biological characteristics of TETs,immunotherapy may bring serious immune-related adverse events(irAE).This paper reviewed the clinical studies and case reports of ICIs in the treatment of advanced TETs at home and abroad in recent years,focusing on the efficacy of ICIs and irAEs in the treatment of advanced TETs,so as to provide additional strategies for the treatment of advanced TETs.
Objective To analyze the influence of the extract of Shancigu(appendiculate cremastra pseudobulb)on the migration and invasion ability of human colorectal cancer SW480 cell and its molecular mechanism.Methods The human colorectal cancer SW480 cell was selected and divided into blank control group,Shancigu groups of different concentra-tions(200 mg·L-1,400 mg·L-1),and 5-Fu group(10 μmol·L-1).The scratch experiment,cell proliferation inhibition ex-periment,cell migration and invasion experiment were performed to understand the migration and invasion ability of each group of human colorectal cancer SW480 cells.At the same time,the AEG-1 gene in SW480 cells was silenced by cell transfection technology,and the effect of AEG-1 gene silencing on the expression of various proteins in SW480 cells was understood by Western blotting detection.The expression changes of various proteins in SW480 cells treated with differ-ent concentrations of Shancigu extract was also observed.Results Compared with the blank control group,the wound heal-ing rate,cell migration rate and invasion rate of SW480 cells in different concentrations of Shancigu groups and 5-Fu group were significantly decreased,and the cell growth inhibition rate was significantly increased(P<0.05).The inhibition effect of Shancigu extract on the proliferation and invasion of rectal cancer cells was similar to that of 5-Fu.The inhibition effect on the migration and invasion rate of SW480 cells was concentration-dependent with Shancigu treatment,and the inhibition rate of cell proliferation was concentration-and time-dependent with Shancigu treatment.The expression levels of AEG-1,MMP-2 and MMP-9 proteins were significantly decreased in SW480 cells in the Shancigu groups and the 5-Fu group,and the expression level of E-cadherin protein was significantly increased(P<0.05).Conclusion The Shancigu extract may inhibit the migration and invasion of human colorectal cancer SW480 cells by inhibiting the expression of AEG-1 protein,up-regulating the expression of E-cadherin protein,and down-regulating the expression of MMP-2 and MMP-9 protein.
Objective To construct and implement the clinical application regulatory strategy of anti-tumor drugs ac-cording to SWOT analysis results,and evaluate its application effect,so as to provide reference and basis for the manage-ment of clinical application of anti-tumor drugs.Methods The data of 600 discharged patients whose medical orders in-volved the use of anti-tumor drugs were randomly selected before and after the implementation of the regulatory strategy.The changes in the rationality of clinical application of anti-tumor drugs before and after the implementation of the regulato-ry strategy were analyzed and compared.Results After the implementation of the strategy,the irrational clinical application of anti-tumor drugs in our hospital was significantly improved,especially in the non-tumor departments with serious irratio-nal drug use in the past and in the common types of irrational drug use in the past,such as unreasonable drug dosage,un-reasonable solvent dosage,unreasonable order of drug administration,etc.The irrational rate of medication decreased from 19.5%before intervention to 10.2%after intervention,and the difference was statistically significant(P<0.05).Conclusion The construction and implementation of the regulatory strategy for clinical application of anti-tumor drug is conducive to its rational and standardized use.
Objective To investigate the prognostic value of the interleukin-26(IL-26)expression in tissues of hepato-cellular carcinoma(HCC)patients after hepatectomy.Methods The clinical data were analyzed retrospectively of 120 HCC patients who were admitted to the Haikou Affiliated Hospital of Xiangya School of Medicine,Central South University be-tween Jan 2011 and Dec 2014.The expression of IL-26 was detected by immunohistochemical staining.According to the expression levels of IL-26,the patients were divided into IL-26 low expression group(n=62)and IL-26 high expression group(n=58).The relationship between the expression level of IL-26 and the clinicopathological characteristics and prog-nosis was analyzed.Cox proportional risk model was used to analyze the prognostic factors of HCC patients.Results The ex-pression of IL-26 in HCC was correlated with the tumor diameter>5 cm,microvascular invasion and TNM stage Ⅲ-Ⅳ(χ2= 11.100,P=0.001;χ2=11.257,P=0.001;χ2=6.541,P=0.011).Univariate Cox regression analysis showed that high expres-sion of IL-26,AFP>50 ug/L,tumor diameter>5 cm,macrovascular invasion and microvascular invasion were associated with the recurrence-free survival(RFS)and overall survival(OS)of HCC patients.Multivariate Cox regression analysis showed that high expression of IL-26,tumor diameter>5 cm and microvascular invasion were independent risk factors of RFS in HCC patients(P<0.05),and that high expression of IL-26 and microvascular invasion were independent risk factors of OS in HCC patients(P<0.05).Kaplan-Meier survival curve showed that the 5-year RFS and OS of patients with low IL-26 expression were higher than those of patients with high IL-26 expression(χ2=11.002,P=0.001;χ2=8.832,P=0.007).Conclusion The prognosis was poor in HCC patients with high expression of IL-26.The expression level of IL-26 in tissues may be a new prognostic indicator and a target for vascular therapy in HCC patients.
Objective To investigate the mechanism of transducin(β)-like 1 X-linked receptor 1(TBL1XR1)promoting the migration and invasion of ovarian cancer cell by upregulating the Wnt/β-catenin signaling pathway.Methods Differen-tial expression of TBL1XR1 in ovarian cancer and normal ovarian tissues was assessed by using the Gene Expression Profil-ing Interactive Analysis(GEPIA 2),immunohistochemistry and Western blotting methods.The correlation between TBL1XR1 and overall survival of ovarian cancer patients in the Cancer Genome Atlas(TCGA)database was evaluated.The GO and KEGG enrichment analysis of differentially expressed genes(DEG)between TBL1XR1 high and low expression groups were also performed to explore their bioinformatic functions.Wound healing assay and Transwell stromal gel inva-sion assay were used to determine the effect of TBL1XR1 on the migration and invasion ability of ovarian cancer cells,re-spectively.Rescue experiments were performed with Wnt3a,an activator of the Wnt/β-catenin signaling pathway.Western blotting was used to detect changes in Wnt/β-catenin signaling pathway protein expression levels after knockdown or over-expression of TBL1XR1.The effect of TBL1XR1 on the changes of Wnt/β-catenin signaling pathway activity was detected by TOP/FOP luciferase reporter assay.Results The expression level of TBL1XR1 in ovarian cancer tissues was higher than that in normal ovarian tissues,and the overall survival of ovarian cancer patients in the low expression group was higher than that in the high expression group.The results of GO analysis and KEGG analysis suggested that the biological func-tions of TBL1XR1 were related to hormone transport,hormone secretion,regulation of hormone secretion and peptide trans-port,and neuroactive ligand-receptor interactions.Knockdown of TBL1XR1 significantly inhibited the migration and inva-sion of ovarian cancer cell,and this effect could be reversed by Wnt3a.Overexpression of TBL1XR1 significantly increased the migration and invasion ability of ovarian cancer cells.When TBL1XR1 expression was downregulated,the activity of Wnt/β-catenin signaling pathway and its protein expression levels were subsequently reduced.Conclusion TBL1XR1 was highly expressed in ovarian cancer and was associated with the poor prognosis of ovarian cancer patients.TBL1XR1 could promote the migration and invasion of ovarian cancer cells by upregulating Wnt/β-catenin signaling pathway.It may play an important role in the tumorigenesis and development of ovarian cancer as a tumor promoter.
